The CCIB seminar series offers interesting presentations related to research in computational and integrative biology. The presentations reflect the types of collaborative research being done at the center and provide an opportunity to come together as a community for informal discussions and conversation.
Unless noted, all seminars take place during the free period (12:20pm – 1:20pm) in Armitage Hall, 3rd Floor Faculty Lounge.
Coffee and snacks are provided.
Dr. Jinglin Fu
Dept. of Chemistry
Tuesday, September 17th, 2013
12:30pm – 1:20pm
Faculty Lounge, Armitage Hall
Spatially Interactive Biomolecular Networks Organized by Nucleic Acid Nanostructures
The cellular activities of all organisms are governed by a variety of multi-step chemical conversion events, or biochemical pathways that exhibit extraordinary yield and specificity. Biological systems have evolved numerous mechanisms to regulate this process including molecular scaffolding and spatial confinement, where the function of a pathway is critically dependent on the relative position, orientation, and quantity of participating enzymes. Understanding the effect of spatial arrangement on pathway activity in multi-enzyme systems will not only advance our knowledge of fundamental biomolecule networks, but is also important to translate biochemical reaction pathways to non-cellular environment applications. Toward this goal, DNA nanostructures, that pieces of DNA can come together and spontaneously assemble into sophisticated structures, have been employed as assembly scaffolds to organize multiple enzymes with precisely-controlled spatial positions and orientation. This makes it possible to investigate and mimic several important mechanisms for multi-enzyme pathways, including the dependence of the distance between the enzymes on the overall reaction rate and specificity
(Fig.1A), the ‘Swing Arm’-organized substrate channeling (Fig.1B) and the regulatory enzymatic circuitry (Fig.1C). These approaches and principles provide a predictable framework to create efficient and regulatory nanoscale catalytic complexes, which will find utility in the development of the catalysts for chemical synthesis, bioenergy, diagnostic and therapeutic applications.
Dr. Luca Larini
Dept. of Physics
Thursday, September 19th, 2013
12:30pm – 1:20pm
Lecture Hall, Science Building
Bridging length and time scales in complex materials
Complex systems (such as biomolecules or glasses) are characterized by multiple time and length scales that are associated with different properties of the system under examination. As a consequence, simplified models (referred to as coarse-grained models) can be constructed that retain only the most relevant physical properties at a given scale. These models can be expected to render both theory and simulations more tractable. In this talk I will present examples of successful coarse-grained models and techniques applied to glass transition, biomolecules and simple liquids. These examples will be used to introduce basic notions of the theory and the algorithms employed in multiscale modeling.
Dr. Eric Klein
Dept. of Biology
Tuesday, September 24th, 2013
12:30pm – 1:20pm
Mechanical signaling pathways in bacteria
The dynamic regulation of virulence is an essential aspect of pathogenesis that holds great promise for combating infectious disease. While the overwhelming emphasis of the field to date has been on the chemical cues that mediate bacteria-host interactions, there is evidence indicating that bacteria can also sense and respond to their mechanical environment. In particular, I have demonstrated that uropathogenic Escherichia coli (UPEC) induce a novel gene expression program in response to adhesion to stiff surfaces. While the mechanism by which fimbriae attach to their targets is well understood, little is known about how fimbrial attachment may trigger pathogenic gene expression. Using a variety of genetic and microscopy-based approaches, my work will focus on how mechanical forces stimulate adhesion-mediated gene expression, the mechanism of bacterial mechanotransduction, and the role of mechanical signaling in pathogenic infection. Ultimately, my goal is to identify components of the mechanotransduction pathway as targets for the development of novel therapeutics for use as alternatives to traditional antibiotics.
Dr. Laura Scheinfeldt
Coriell Institute for Medical Research
Coriell Personalized Medicine Collaborative
Thursday, September 26th, 2013
12:30pm – 1:20pm
Lecture Hall, Science Building
An integrated genomic approach to the study of human adaptation to high altitude
The recent availability of genomic data and related methodologies has resulted in several genome-wide studies of human adaptation across geographically diverse populations. Such studies have provided novel candidate genes and pathways putatively involved in adaptation to different environments, and in particular, to high altitude. However, one of the limitations of these studies is the high false positive rate for candidate loci, and additional work is needed to translate the strongest results into biologically interpretable adaptive candidate variants. I will discuss methods that may help to recover biological signals of adaptation to high altitude in Ethiopia and ways in which I have incorporated complementary phenotypic data. I will also present results from studies of other high altitude regions across the world and discuss the combined findings.
Dr. Paolo Zunino
Department of Mechanical Engineering and Materials Science
University of Pittsburgh
Thursday, October 10th, 2013
12:30pm – 1:20pm
Lecture Hall, Science Building
Computational models for fluid and chemical exchange between microcirculation and tissue interstitium
Reduced models of fluid flow or mass transport in heterogeneous media are often adopted in the computational approach when the geometrical configuration of the system at hand is too complex. A paradigmatic example in this respect is blood flow through a network of capillaries surrounded by a porous interstitium. We numerically address this biological system by a computational model based on the Immersed Boundary Method (IBM), a technique originally proposed for the solution of complex fluid-structure interaction problems. Exploiting the large aspect ratio of the system, we avoid resolving the complex 3D geometry of the submerged vessels by representing them with a 1D geometrical description of their centerline and the resulting network [1,2].
Cancer employs mass transport as a fundamental mechanism of coordination and communication and the physics of mass transport within body compartments and across biological barriers differentiates cancer from healthy tissues . Mass transport is also at the basis of cancer pharmacological treatment Delivery of diagnostic and therapeutic agents differs dramatically between tumor and normal tissues. In contrast to healthy tissue, tumors exhibit interstitial hypertension, which is caused by the high permeability of tumor vessels in combination with the lack of functional lymphatic vessels in the tumor interstitial space.
The analysis of fluid and chemicals exchange in vascularized tumors is a relevant application of the model proposed here. We will use it to study fluid and mass exchange between the capillaries and the interstitial volume, as well as to compare different modalities to deliver chemotherapy drugs to the tumor mass, including using nanoparticles as delivery vectors.
 D’Angelo, C., Quarteroni, A. On the coupling of 1D and 3D diffusion-reaction equations. Application to tissue perfusion problems (2008) Mathematical Models and Methods in Applied Sciences, 18 (8), pp. 1481-1504.
 L.Cattaneo, P.Zunino, Computational models for fluid exchange between microcirculation and tissue interstitium. Networks and Heterogeneous Media (2013). MOX Report 25/2013
 Baxter, L.T., Jain, R.K. Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection (1989) Microvascular Research, 37 (1), pp. 77-104.
Thursday, October 17, 2013
12:30 – 1:20 pm
Science Lecture Hall, Science Building
Patterns of microRNA changes in Aging and Neurodegeneration
microRNAs (miRNAs) are 20~24nt small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity in length and sequences in different biological contexts. Here, by examining the expression pattern of miRNAs by northern blot analysis, we found that Drosophila miRNAs show distinct isoform pattern changes with age. Surprisingly, an increase of some miRNAs reflects increased 2′-O-methylation of select isoforms. Small RNA deep-sequencing revealed a global increase of miRNAs loaded into Ago2, but not into Ago1, with age. In addition, only specific miRNA isoforms showed increased loading into Ago2, but not Ago1, indicating a mechanism for differential loading of miRNAs between Ago1 and Ago2 with age. Mutations in Hen1 and Ago2, which lack 2′-O-methylation of miRNAs, result in accelerated neurodegeneration and shorter lifespan, suggesting an impact of the age-associated increase of 2′-O-methylation of small RNAs on age-associated processes. Our study highlights that miRNA 2′-O-methylation at the 3′end is modulated by differential partitioning of miRNAs between Ago1 and Ago2 with age, and that this process might impact age-associated processes in Drosophila
Dr. Wei Xu
Department of Oncology
McArdle Laboratory for Cancer Research
University of Wisconsin
Thursday, October 24th, 2013
12:30pm – 1:20pm
Lecture Hall, Science Building
Developing in vitro and in vivo models for probing environmental estrogens’ action via estrogen receptor dimers
Many environmental estrogens so called xenoestrogens mimic the action of endogenous estrogens to regulate the risk of breast cancer. The effects of xenoestrogens are mediated by functional estrogen receptor dimers. Although numerous biochemical evidence exist in support of ERa/b heterodimer formation, the functions of heterodimers were completely unknown.
We have developed Bioluminescence Resonance Energy Transfer (BRET) assay to study intermolecular interactions of ERa/b heterodimers. Further, this assay was used for high throughput screening and identified several ERa/b heterodimer inducing compounds.
These compounds allow us to reveal the growth inhibitory function of ERa/b heterodimers and in silico modeling identifies possible pharmacophore conferring ERa/b selectivity. Finally, I will discuss recent animal models developed to screen ligands specific to ERa and ERb in vivo.
William J. Welsh, Ph.D.
N. H. Edelman Professor in Bioinformatics
Department of Pharmacology
Robert Wood Johnson Medical School
Tuesday, October 29th, 2013
12:30pm – 1:20pm
Faculty Lounge, Armitage Hall
Computational Approaches to Accelerate Drug Discovery
The recent emergence of the translational medicine paradigm has imposed a high premium on advanced computational platforms to accelerate the discovery of new diagnostic and therapeutic agents. We thus introduce two computational tools, Shape Signatures and Avalanche, developed in the Welsh laboratory that offer a central portal for drug discovery, virtual screening of chemical libraries, and predictive toxicology. Among their many attractive features, Shape Signatures and Avalanche are extremely fast, are accessible via a user-friendly GUI, and can handle any number and type of molecular species. Our current Shape Signatures and Avalanche chemical databases comprise over 3 million commercially available organic compounds including natural products and FDA-approved small molecule drugs. I will present Case Studies, taken from my research laboratory, to demonstrate the utility of Shape Signatures and Avalanche within an integrated drug discovery project. Examples will be drawn from projects aimed at the discovery of novel treatments for cancer, pain, and infectious, as well as cosmetic agents.
Center for Computational & Integrative Biology
Thursday, October 31st, 2013
12:30pm – 1:20pm
Science Building, Lecture Hall
Insights into Glacial Ecosystem using Metagenomics
The temperature in the Arctic region has been increasing in the recent past accompanied by melting of its glaciers. We took a snapshot of the current microbial inhabitation of an Alaskan glacier (which can be considered as one of the simplest possible ecosystems) by using metagenomic sequencing of 16S rRNA recovered from ice/snow samples. Somewhat contrary to our expectations and earlier estimates, a rich and diverse microbial population of more than 2,500 species was revealed including several species of Archaea that has been identified for the first time in the glaciers of the Northern hemisphere. The most prominent bacterial groups found were Proteobacteria, Bacteroidetes, and Firmicutes. Firmicutes were not reported in large numbers in a previously studied Alpine glacier but were dominant in an Antarctic subglacial lake. Principal component analysis of nucleotide word frequency revealed distinct sequence clusters for different taxonomic groups in the Alaskan glacier community and separate clusters for the glacial communities from other regions of the world. Comparative analysis of the community composition and bacterial diversity present in the Byron glacier in Alaska with other environments showed larger overlap with an arctic soil than with a high arctic lake, indicating patterns of community exchange and suggesting that these bacteria may play an important role in soil development during glacial retreat.
Dr Bing Yan
School of Chemistry and Chemical Engineering
Shangdong University, China
Thursday, November 7th, 2013
12:30pm – 1:20pm
Faculty Lounge, Armitage Hall
Modulation of the Biological Activities of Nanoparticles
Nanomaterials are widely used in various industrial sectors, biomedicine, and more than 1300 consumer products. Although there is still no unified safety regulation, their potential toxicity is a major concern worldwide. We discovered that nanoparticles target and enter human cells, perturb cellular signaling pathways, affect various cell functions, and cause malfunctions in animals. Because the majority of atoms in nanoparticles are on the surface, chemistry modification on their surface may change its biological properties significantly. We modified nanoparticle surface using a nano-combinatorial chemistry approach. Novel nanoparticles were discovered to possess reduced toxicity, enhanced cancer targeting ability, or increased cell differentiation regulation. Quantitative nanostructure-activity relationships (QNAR) models have been built and applied for predicting biocompatible nanoparticles.
Thursday, January 24, 2013, Science Building Lecture Hall
Extracting Essential Features of Biological Signaling Networks
Speaker: Dr Natalie Arkus, Postdoctoral Fellow, Department of Physics and Astronomy, University of Pennsylvania
Abstract: Because biological signaling networks have many components, it has become common to model such networks using large systems of coupled ordinary differential equations. However, there is as yet no simple way of determining how solutions to large systems depend on their parameters. In contrast, large systems of differential equations describing electronic circuits are routinely reduced to simpler systems that quantitatively capture circuit behavior using lumped parameters for resistance, capacitance, and inductance. We show that biological signaling networks can similarly be reduced to systems involving a few equations and effective parameters. The effective parameters lump the system’s many components together, yielding a simplified system that contains within it information on all of the many components. We apply this method to a model from the literature of heat shock response in E. coli consisting of 31 equations and 48 parameters. We reduce this model to just 1 equation and 3 effective parameters. The reduced system quantitatively agrees with the original, and demonstrates that feedback loops do not necessarily confer a faster heat shock response at lower cost, as had been claimed. We discuss the application of this method to other models from recent literature, such as that of Beta-catenin degradation in the Wnt signaling network – where a model of 19 equations is reduced to 1-3 equations (depending on the initial conditions), and the features that determine the rate of beta-catenin degradation are extracted.
Tuesday, January 29, 2013, Armitage Hall Faculty Lounge
A Control Theory Approach to Engineering Biomolecular Networks
Speaker: Dr Domitillo del Vecchio, W. M. Keck Career Development Professor in Biomedical Engineering, Associate Professor, Laboratory for Information and Decision Systems (LIDS), Department of Mechanical Engineering, MIT
Abstract: The past decade has seen tremendous advances in the fields of Systems and Synthetic Biology to the point that de novo creation of simple biomolecular networks, or “circuits”, in living organisms to control their behavior has become a reality. A near future is envisioned in which re-engineered bacteria will turn waste into energy and kill cancer cells in ill patients. To meet this vision, one key challenge must be tackled, namely designing biomolecular networks that can realize substantially more complex functionalities than those currently available.
A promising approach to analyzing or designing complex networks is to modularly connect simple components whose behavior can be isolated from that of the surrounding modules. The assumption underlying this approach is that the behavior of a component does not change upon interconnection. This is often taken for granted in fields such as electrical engineering, in which insulating amplifiers enforce modular behavior by suppressing impedance effects. This triggers the fundamental question of whether a modular approach is viable in biomolecular circuits. Here, we address this research question and illustrate how, just as in many mechanical, hydraulic, and electrical systems, impedance-like effects are found in biomolecular systems. These effects, which we call retroactivity, dramatically alter the behavior of a component upon interconnection. We illustrate how, similarly to what is performed in electrical networks, one can reduce the description of an arbitrarily complex system by calculating equivalent retroactivities to the input. By merging disturbance rejection and singular perturbation techniques, we provide an approach that exploits the structure of biomolecular networks to design insulating amplifiers, which buffer systems from retroactivity effects. We provide experimental demonstration of our theory on a reconstituted protein modification cycle extracted from bacterial signal transduction and on a synthetic biology circuit in vivo.
Thursday, February 14, 2013, Science Building Lecture Hall
The Tox21 Program
Speaker: Menghang Xia, Ph.D., Group Leader, Cellular Toxicity & Signaling, NIH Chemical Genomics Center
Abstract: To meet the needs of toxicity testing in the 21st century, the National Toxicology Program (NTP), the NIH Chemical Genomics Center (NCGC), the U.S. Environmental Protection Agency (EPA), and the U.S. Food and Drug Administration (FDA) formed the Tox21 partnership. The goals of Tox21 are to identify mechanisms of compound action at the cellular level, prioritize chemicals for further toxicological evaluation, and develop useful predictive models of in vivo biological response. In the presentation, I will describe the Tox21 program, qHTS-based compound testing and the various Tox21 screening assays that have been validated and screened at the NCGC.
Thursday, March 7, 2013, 12:20pm – 1:20pm, Lecture Hall, Science Building
Patterning challenges for optional sex: the case of reproductive polyphenism in aphids
Speaker: Dr Gregory Davis, Assistant Professor, Biology, Bryn Mawr College
Abstract: The pea aphid, Acyrthosiphon pisum, exhibits several environmentally cued, discrete, alternate phenotypes (polyphenisms) during its life cycle. In the case of the reproductive polyphenism, differences in day length determine whether mothers will produce daughters that reproduce either sexually by laying fertilized eggs (oviparous sexual reproduction), or asexually by allowing oocytes to complete embryogenesis within the mother without fertilization (viviparous parthenogenesis). Oocytes and embryos that are produced asexually develop more rapidly, are yolk-free, and much smaller than oocytes and embryos that are produced sexually. Perhaps most striking, the process of oocyte differentiation is truncated in the case of asexual/viviparous development, potentially precluding interactions between the oocyte and surrounding follicle cells that might take place during sexual/oviparous development. Given the important patterning roles that oocyte-follicle cell interactions play in Drosophila, these overt differences suggest that there may be underlying differences in the molecular mechanisms of pattern formation. We have found differences in the expression of torso-like, as well as activated MAP kinase, suggesting that there are important differences in the hemipteran version of the terminal patterning system between viviparous and oviparous development. Establishing such differences in the expression of patterning genes between these developmental modes is a first step toward understanding how a single genome manages to direct patterning events in such different embryological contexts.
Wednesday, March 27, 2013, Campus Center Multi-Purpose Room
Fast Algorithms for Brownian Dynamics Simulation with Hydrodynamic Interactions
Speaker: Dr Shidong Jiang, Associate Professor, Department of Mathematical Sciences, New Jersey Institute of Technology
Abstract: In the Brownian dynamics simulation with hydrodynamic interactions, the motion of the Brownian particles can be described via a stochastic differential equation (SDE). The change of the displacement vectors of Brownian particles in the popular Ermak-McCammon algorithm for Brownian dynamics simulation consists of two parts: a deterministic part which is proportional to the product of the Rotne-Prager-Yamakawa (RPY) tensor and the given external forces; and a hydrodynamically correlated random part whose covariance is proportional to the RPY tensor. For an arbitrary N-particle configuration, the computation cost of the classical algorithms for computing the deterministic part is quadratic in N; and the computational cost for generating random vectors with a specific covariance is cubic in N. These form the bottleneck for long term large-scale Brownian dynamic simulation.
In this talk, we will first present two fast multipole methods (FMM) for computing the deterministic part. We then discuss several methods of generating random vectors whose covariance matrix is proportional to the RPY tensor. The performance of our algorithms will be illustrated via several numerical examples. The algorithms are expected to be useful for the study of diffusion limited reactions, polymer dynamics, protein folding, and particle coagulation.
This is joint work with Zhi Liang at NJIT, Zydrunas Gimbutas & Leslie Greengard at NYU, & Jingfang Huang at UNC at Chapel Hill.
Thursday, March 28, 2013, 12:20pm – 1:20pm, Lecture Hall, Science Building
Mathematical Models for Cancer Treatments – The Role of the Vasculature and the Immune System in Optimal Protocols for Cancer Therapies
(joint research with Urszula Ledzewicz, Southern Illinois University)
Speaker: Dr Heinz Schättler, Dept. of Electrical and Systems Engineering, Washington University, St Louis
Abstract: A systematic study of cancer treatments requires that we take into account not only the tumor and its growth, but also its microenvironment which comprises the cancerous cells, (sensitive and resistant to the treatment), healthy cells, tumor vasculature, immune system and more. In this talk, I will discuss some mathematical models that include increasingly more complex aspects of the tumor microenvironment such as tumor heterogeneity, angiogenic signaling, and tumor immune system interactions. These models will be analyzed from a dynamical systems point of view in the context of the optimal control problem of designing treatment protocols. Using methods of geometric optimal control, syntheses of optimal solutions will be described for some of these models. As more and more aspects of the tumor microenvironment are taken into account, optimal solutions change from bang-bang solutions (which correlate with the standard medical practice of giving chemotherapeutic agents in maximum tolerated doses) to administration schedules that favor singular controls (which administer agents at specific time varying reduced dose rates). This raises the possibility of metronomic administrations of agents (at low concentrations over prolonged periods without any major interruptions), an alternative scheduling approach that has shown some success in pediatric cancers. The talk will also address some of the mathematical challenges that arise in the analysis of these generally highly nonlinear, multi-input control systems.
2011 – 2012 Seminars:
Monday, December 12, 2011, (BSB 334)
Characterization of ultradian rhythms in adult male rats through EEG analyses and in Neuorspora crassa through growth data analyses
Speaker: Steve Moffett, Ph.D. candidate, CCIB, Rutgers University
Abstract: The brain gives rise to rhythms on different time scales, including circadian or ultradian. In humans, hormone secretion is known to follow an ultradian rhythm of approximately 90 minutes. To date, ultradian rhythms have not been well-characterized in rodents. Adult male rats were prepared with electrodes for electroencephalography (EEG) and in the neck musculature for electromyography. After recovery, the EEG signal was recorded for 48-hours in a 12/12 L/D cycle. Following data acquisition, a window fast-Fourier transform (FFT) of EEG data was computed for 30-second epochs. The percentages of total power in 1-4 Hz, 4-8 Hz, or 1-8 Hz frequency bands were separately plotted by epoch over the course of the study. An ultradian rhythm in percent total power was apparent in the plots for each of the frequency ranges. To quantitate the ultradian rhythm, trained observers independently determined the time of occurrence of local minima in the window FFT plot. The means of measurements of periods between minima for given observers ranged from 9.4 to 13.2 minutes. A similar study was conducted on the growth data of the model circadian organism Neurospora crassa.
February 6, 2012
Systematic Structural Mass Spectrometry: Probing Structures of Membrane Skeletons Using Chemical Crosslinking, Mass Spectrometry and Homology Modeling
Speaker: David W. Speicher, Ph.D., Casper Wistar Professor in Computational and Systems Biology
Director, Center for Systems and Computational Biology, The Wistar Institute
Abstract: Crystallographic and NMR techniques have produced high resolution structures of many protein domains, small proteins and some protein complexes. However, few high resolution structures exist for proteins or protein complexes larger than 100 kDa, and no high resolution structures exist for the majority of proteins expressed by the human genome. A strategy for systematically determining novel protein structures is to use homology modeling since one or more high resolution structures exist for most protein folds. However, major challenges include: distinguishing between multiple plausible models, improving accuracy of predicted models, and experimental validation of models. A few distance constraints from chemical crosslinks, particularly “zero-length” linkers, can effectively address all of these challenges, and recent advances in tandem mass spectrometry (MS/MS) have improved in-depth analysis of complex peptide mixtures. Despite these advances, chemical crosslinkers remain under-utilized because there are no effective software tools for identification of peptides crosslinked by zero-length crosslinkers. While analysis of small proteins and protein complexes can be performed through manual review of the MS/MS data, this approach is very time consuming and tedious for moderate-sized proteins and impractical for large proteins and protein complexes. To address this roadblock, we recently developed software and a multi-tiered MS/MS analysis strategy that eliminates subjective, tedious manual review of MS/MS data, identifies more crosslinks, increases the confidence of crosslink assignments, and enables analysis of much larger proteins and protein complexes. We are applying this strategy to the systematic analysis of spectrin and other protein complexes in the membrane skeleton, a two-dimensional network on the cytoplasmic face of the membrane that provides membrane flexibility and integrity in red cells as well as other cell types. A long term goal is the development of a comprehensive medium resolution structure for the entire red cell membrane skeleton.
March 19, 2012
What I Saw When I Watched Some Evolution
Speaker: Dr. Michael Desai, Assistant Professor, Department of Organismic and Evolutionary Biology, Harvard University
Abstract: Evolutionary adaptation proceeds by the accumulation of beneficial mutations. We often think of these beneficial mutations as being rare, and adaptation is then characterized by a sequence of “selective sweeps”: a beneficial mutation occurs, spreads through an entire population, then later another beneficial mutation occurs, and so on. This simple picture is the basis for much of our intuition about adaptive evolution, and underlies a number of practical techniques for analyzing sequence data. Yet many large and mostly asexual populations — including a wide variety of unicellular organisms and viruses — live in a very different world. In these populations, beneficial mutations are common, and frequently interfere or cooperate with one another as they all attempt to sweep simultaneously. This radically changes the way these populations adapt: rather than an orderly sequence of selective sweeps driven by single strongly beneficial mutations, evolution is a constant swarm of competing and interfering mutations. The fate of any individual mutation depends on how it interacts with this background of other variation; no single mutation drives adaptation by itself. I will describe a new experimental system developed to directly visualize some aspects of these dynamics, and describe the results of 1000 generations of experimental evolution of 600 budding yeast populations. We see intriguing signatures of complicated patterns of interference between mutations, as well as the unexpected spontaneous evolution of stable polymorphisms in some populations. I will describe some further experiments to show how this dynamics depends on factors such as population subdivision and patterns of epistasis. If time allows I will also describe new theoretical work which predicts how many beneficial mutations collectively lead to variation in fitness within the population, and how each mutation interacts with this variation to determine its ultimate fate.
April 9, 2012
Automated Annotation of Chemical Names in the Literature
Speaker: Jun Zhang, PhD, Post-doc with Hao Zhu, Assistant Professor, Chemistry, Rutgers-Camden
Abstract: A significant portion of the biomedical and chemical literature refers to small molecules. The accurate identification and annotation of compound name that are relevant to the topic of the given literature can establish links between scientific publications and various chemical and life science databases. Manual annotation is the preferred method for these works because well-trained indexers can understand the paper topics as well as recognize key terms. However, considering the hundreds of thousands of new papers published annually, an automatic annotation system with high precision and relevance can be a useful complement to manual annotation. An automated chemical name annotation system, MeSH Automated Annotations (MAA), was developed to annotate small molecule names in scientific abstracts with tunable accuracy. This system aims to reproduce the MeSH term annotations on biomedical and chemical literature that would be created by indexers. To reduce the false-positive annotations, MAA incorporated several filters to remove “incorrect” annotations caused by nonspecific, partial, and low relevance chemical names. Accurate chemical name annotation can help researchers not only identify important chemical names in abstracts, but also match unindexed and unstructured abstracts to chemical records. The current work is tested against MEDLINE, but the algorithm is not specific to this corpus and it is possible that the algorithm can be applied to papers from chemical physics, material, polymer and environmental science, as well as patents, biological assay descriptions and other textual data.
Monday, April 23, 2012, 12:10 – 1:10 pm, BSB 117
Modeling and simulations of single-stranded RNA viruses
Speaker: Mustafa Burak Boz, Georgia Institute of Technology, Ph.D. Candidate in Physical Chemistry
Abstract: We investigate the assembly of Satellite Tobacco Mosaic Virus (STMV) using coarse-grained models. We use multi-level coarse-grained representations to decrease the computational expenses and adequately represent the different parts of the viral structure. The RNA coarse-grained model is generated from a proposed secondary structure . The RNA model has one pseudo-atom (bead) per residue. The coarse-grained model for the capsid contains twenty triangular units, each of which also contains three flexible positively charged protein tails. The assembly process as well as the stability of the virus mainly depends on RNA-protein and protein-protein interactions. The protein tails are attracted to the RNA by electrostatic interactions while the capsid proteins are weakly attracted with each other by hydrophobic interactions. We model RNA-protein interactions with a Debye-HÃŒckel potential and protein-protein interaction with a Lennard-Jones potential. We vary values of these two interactions to find regions where the virus is stable and will self-assemble. Finally, we investigate the assembly of the virus using molecular dynamics. These simulations help us understand the individual roles of these two interactions on viral assembly.
Ref: 1. Schroeder JS, Stone, WJ et.al. Biophysical Journal,101: p. 167-175, 2011
Thursday, April 26, 2012, 12:30 – 1:30 pm, Science Bldg, Science Lecture Hall
Investigating functional roles of circadian rhythms in Neurospora crassa employing mathematical modeling and experimental validations
Speaker: Christian Hong, PhD, Assistant Professor, The Department of Molecular & Cellular Physiology, University of Cincinnati
Abstract: Fundamental cellular processes that maintain most organisms’ health and survival include cell cycle, DNA damage response, and circadian rhythms. Cell cycle is equipped with multiple checkpoints for controlled growth, DNA rep-lication, and divisions. DNA damage response (DDR) mechanisms control cell fate by either repairing single or double strand breaks, or triggering apoptosis for programmed cell death when the damage is fatal. Last, but not least, is circadian rhythm that keeps track of time of a day, and plays a central role in most organ-isms for setting the sleep/wake cycle, feeding rhythms, and other daily activities. These distinct molecular mechanisms communicate with each other and create a complex bio-molecular network to optimize conditions for cells to grow and adapt to the surrounding environment. We explore functional roles of circadian rhythms in other cellular processes such as cell cycle employing mathematical modeling and experimental validations using a modeling organism Neurospora crassa.
Monday, April 30, 2012, 12:10 – 1:10 pm
Immune-based identification of drug resistance in Mycobacterium tuberculosis: Shifting a paradigm or tilting at windmills?
Speaker: Gregory P. Bisson, MD, MSCE, Assistant Professor of Medicine and Epidemiology, Division of Infectious Diseases, Senior Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine
Abstract: Nearly 2 billion people, one third of the World’s population, are at risk of active tuberculosis (TB) because they are latently infected with the causative agent Mycobacterium tuberculosis ( Mtb ) , and almost 2 million TB-related deaths occur annually. A major barrier to TB control is that detection of Mtb drug resistance requires collection of microbiological samples, which are not available in many cases of active disease and in all cases of latent infection. Treatment of latent Mtb infection, a necessary approach to global TB control efforts, cannot be properly targeted if drug resistance is suspected, which represents a major knowledge gap. A central tenet of microbiology and infectious diseases holds that identification of antibiotic resistance in human pathogens requires direct access to the organism. In this talk, the hypothesis that the host adaptive cellular immune system responds to changes in the proteome of pathogens that specifically occur as a result of genetic mutation(s) conferring drug resistance will be presented, using rpoB mutation and rifampicin resistance in Mtb as an example. The host immune system is not expected to consistently and specifically recognize epitope differences conferred by SNPs in rpoB , but data from model organisms phylogenetically related to Mtb indicate that rpoB mutation activates dormant gene networks not expressed by wild-type strains. The possibility that Mtb strains share conserved, ancestral responses of competition interference will be considered in light of preliminary proteomics data, and the public health implications of the approach will be discussed
Thursday, June 21, 2012, 1:00pm – 2:00pm, Campus Center – South BC Conference Room
Information Session on Entrepreneurial Collaborations
Speaker: CCIB member faculty in conjunction with several faculty members of the School of Business
Abstract: The CCIB, in conjunction with several faculty members of the School of Business, is sponsoring a one-hour session to address possible collaborations on entrepreneurial endeavors, start-ups, etc., as well as the potential for related graduate course offerings and seminars. All interested parties are welcome to attend.
The format for the meeting would be an initial general conversation on programmatic collaborations. This will be followed by a series of 5-10 minute presentations on projects of CCIB researchers and discussions with the members of the Business School on potential entrepreneurial ventures related to the research. Please reply to Karen Taylor at email@example.com if you would like to make a research presentation at the meeting. RSVP is requested via email to karen if you plan to attend. Thank you.
Monday, June 25, 2012
The Defence Science and Technology Organisation (DSTO) is part of Australia’s Department of Defence and Australian Government’s lead agency charged with applying science and technology to protect and defend Australia and its national interests ( http://www.dsto.defence.gov.au ).
Speaker: Dr Gulay Mann BSc (Hons), Ph.D., Research Advisor to Defence Science Institute, Principal Research Scientist, Human Protection & Performance Division, Defence Science and Technology Organisation, Australia.
Abstract: In January 2002, Dr Mann commenced work with CSIRO Division of Plant Industry at the Black Mountain laboratories in Canberra. Her research activities included: a) The application of molecular/genetic analyses to investigate the genes responsible for complex dough attributes; b) Processing of novel cereal grains for maximum health benefit; c) Genetic basis of wheat quality; d) Development of improved analytical methods for key wheat quality traits; and e) Development of a laboratory scale baking facility. She has written numerous papers and conference proceedings on dough rheology, wheat and end product quality.
Dr Mann joined DSTO’ss Human Protection and Performance Division in February 2006 as an S&T 7 (corresponding to Principal Research Scientist), as Capability Leader of Defence Nutrition and Food Technology. Dr Mann provided scientific leadership for DSTO’ss research programs in Nutrition & Dietetics and Food Science & Technology, and also supervised the management of the freeze dried meal production line.
In March 2009, Dr Mann took up a career development position at the DSTO Headquarters as the Director Strategic Planning and Coordination in Science Strategy and Policy Branch. In this role, she involved in the strategic coordination and science planning across DSTO as well as providing policy advice on the defence science and technology capabilities needed to achieve Defence’s broad objectives and priorities.
Since September 2011, Dr Mann is developing an enabling research program in Synthetic Biology.